Toxicity of nightshade berries (Solanum dulcamara) in mice

Abstract

Ripened nightshade berries (Solanum dulcamara) are among the most commonly reported plant ingestions in Minnesota. Because of the lack of adequate information regarding the toxic qualities of S. dulcamara berries, the ingestion of even small quantities by children is usually treated conservatively with syrup of ipecac. The toxicity of S. dulcamara berries was studied by gavaging mice with a preparation of lyophilized berries, ripened and unripened, collected at various times of the year. Mice receiving unripened fruit from early in the season had gastrointestinal tissue changes consistent with solanine toxicity. Animals dosed with unripened fruit from the latter part of the year showed behavioral signs suggestive of solanine toxicity, however gastrointestinal lesions were not observed. In no case did the ripened fruit produce behavioral or histologic toxicity. Aggressive treatment of children ingesting limited amounts of ripened S. dulcamara berries appears to be unnecessary.

Full text

cLINTCAL
TOXTCOLOGY,
28(2), 185-192
(1990)
1 Based on a presentation at the Annual AACT/AAPCC/ABMT/
CAPCC Scientific Meeting, Atlanta, Georgia, October 14,1989.
2 This work was funded by a Research Award from the American
Association of Poison Control Centers (to C.S.H.).
TOXICITY OF NIGHTSHADE BERRIES
(Solanum
dulcamara)
IN MICE12
Carl S.
Hornfeldt.
B.S.* and
James
E. Collins,
D.V.M., Ph'D.**
Hennepin Regional
Poison
Center,
Hennepin County Medical Center,
Mlnneapolis,
Minnesota*; College
Of Veterinary Medicine,
Universiw of Minnesota,
St. Paul, Minnesota**
ABSTRACT
Ripened nightshade berries (Solanum dulcamara) are among _
the most
commonly r:eported plant ingestions in Minnesota. Because of the lack of
adequate-information regarding the toxic qualities of S. dulcamara berries,
the ingestion of even small quantities by children is usually treated
conservatively with symp of ipecac. The toxicity of S. dUlclryara berries was
studied by gavaging miCe wiih a preparation of lyophilized berries, ripened
and unripened,- collected at various times of the year. Mice receiving
unripened fruit from early in the season
had gastrointestinal tissue changes
consistent with solanine ioxicity. Animals dosed with unripened fruit from
the latter part of the year showed behavioral signs suggestive of solanine
toxicity, however gastrointestinal lesions were not observed. In no case did
the ripened fruii produce behavioral or histologic toxicity. Aggressive
treatment of children ingesting limited amounts of ripened S. dulcamara
berries appears to be unnecessary.

186 HORNFELDT
AND COLLINS
INTRODUCTION
The ingestion of ripened nightshade
berries,
Solanum dulcamara,
Family Solanaceae,
is one of the most common
poisonous
plant exposures
encountered
by the
Hennepin
Regional
Poison Center. Common
names for
S.
dulcamara
include
European
nightshade,
American
nightshade, climbing
nightshade, deadly nightshade, woody nightshade, blue nightshade,
bittersweet, bitter nightshade,
European
bittersweet,
poison
berry
and
snake
berry (1-6). S. dulcamara
is in the same
genus
as black nightshade
(S.
nigrum)
(1,3-6)
and
the
potato,
(S.
tuberosum)
(1-6), plants known to contain
a variety of potentially
toxic glycoalkaloids
and alkamines
(7), collectively
known
as
solanine
(4).
Although solanine
production is independent of photosynthesis
(8),
most reported cases of solanine
poisoning
are
limited to ingestion
of green
plant material. For example,
potato tubers
(S. tuberosum)
are not only
nontoxic
but an important food source.
However,
green potato
tubers
and
potato
sprouts are
responsible
for many solanine
poisonings
(9-11). As the
green
fruit of black nightshade
(S. nigrum) as
well as other plants in the
genus
Solanum
ripen, they
appear to lose their toxicity
('l',2,6).
In addition,
other
members of the
family
Solanaceae
known to contain
solanine
alkaloids
bear nontoxic fruit. Thus, the ripened fruit of the tomato (Lycopersicon
esculentum)
and the ground
cherry
(Physalis
longifolia) are edible
(3,4).
In contrast,
it is generally
assumed that S. dulcamara
berries
are
poisonous,
although their toxicity is poorly documented
(5,6). In two
reported cases of human
poisoning
the quantity
and identity of the berries
was
not known with certainty
(I2) and
green leaves
as
well as
berries
were
also
involved
(13). Considering
how
frequently these berries
are eaten,
the
scarcity
of reported cases of poisoning from nightshade berries seems
remarkable.
For example,
109
exposures
were
reported
in Minnesota
alone
in 1986
(14), primarily in children
under six
years
of age. Because specific
information
regarding the toxicity
of ripened
nightshade berries
is lacking,
the majority of ingestions encountered by this poison center treatqd
conservatively
with ipecac-induced emesis, even
when the ingestion
is small.
TOXICITY OF NIGI
The aim of this
fulcamara are ct
treatment follow
Because
1
solanine
toxicity
approximatelY
3(
or four and givt
throughout
the s
In the ini
fokalnat:a berri(
several
locations
fruit were
carefr
of other solanac
were frozen
an
resulted
in apP
residual particl
through an 18
NY). Two grt
of either riPer
normal saline.
3.33
red
beni,
as a control.
made to blit
animals.
After
necropsied.
I
were immed;
paraffin, secl
and examine

INS TOXICITY OF NIGHTSHADE
BERRIES IN MICE t87
The
aim of this study
was to determine whether
the ripened
berries
of s.
dulcamara are capable
of producing
toxicity, thereby
clarifying
the need
for
treatment
following
accidental ingestion.
METHODS
Because
previous
work has shown that rodents
are susceptible
to
solanine
toxicity
(15,16),
male,
five week-old
Swiss-Webster
mice weighing
approximately
30
grams
were
used. Animals
were housed in groups
of three
or four and given
standard laboratory
rodent chow and water ad libitum
throughout
the study
period.
In the initial phase
of this study, fully ripened,
as well as green,
S.
dulcamara
berries
were
collected
during the last
week
of August,
1988 from
several locations
in St. Paul,
Minnesota.
Leaves,
stems and
partially
ripened
fruit were carefully removed. As previous
work has
shown that the toxicity
of
other
solanaceous
plants
is not lost
during lyophilization (16),
the berries
were frozen
and lyophilized
(FTS Systems, Inc., Stone Ridge,
NY). This
resulted
in approximately
a 757o loss
in weight. After being finely
ground,
residual particles
were filtered so that the resultant powder
would pass
through an 18
gauge
gavage
needle
(Popper
& Sons, Inc., New Hyde Park,
NY). Two groups,
consisting
of 12 mice
each,
were gavaged
with 8 gm/kg
of either
ripened
or unripened
berry material
reconstituted
to one ml with
normal
saline. This
dose of dried material
represents 4.36
greenberries
and
3.33
red berries. A third group
was
gavaged
with normal
saline
and served
as a control. All three
groups
were
treated
simultaneously. No attempt was
made
to blind the observer
performing
the behavioral
analysis of the
animals.
After 24 hours, six animals from each group were euthanized and
necropsied.
Portions
of liver,
stomach,
duodenum,
jejunum,
cecum and colon
were
immediately fixed in 10Vo
neutral buffered formalin, embedded in
paraffin,
sectioned
at 4 p,M
thickness,
stained using hematorylin
and eosin,
and examined for lesions
consistent
with solanine toxicity
(16).
rafa,
ures
; for
bing
ade,
rake
) (s.
rtain
ively
,(8),
reen
only
and
; the
L
the
tion,
ioids
icon
).
are
two
:ries
vere
the
ems
one
:ific
irg,
rted
tall.

188 HORNFELDT
AND COLLINS
The second
phase
of this study was conducted
in a similar manner
except that unripened fruit were collected during the last
week of June,
1989
and ripened
and unripened
fruit were also
gathered
during the last week of
July, 1989. Three animals from each of these three groups
and a control
group
were necropsied
as
previously
described.
These
studies were performed
with the approval of the Animal Care
and
Use Committee
of the University of Minnesota whose
guidelines for the
care and use of laboratory
animals were strictly
followed.
RE,SULT'S
During
the initial phase
of the study, 3 of 12
animals receiving
green
berry material
had
signs of labored
breathing
and
lethargy
approximately
five
hours
after
the inoculation.
After 24 hours,
all mice in this
group
developed
rough hair coats. In contrast, the mice receiving ripened S. dulcamara
berries
and control animals remained
free of signs of toxicity until the end
of the study
period. However,
necropsy
of mice in each treatment group
did not reveal
tissue changes
when compared
to control animals.
In the second
phase,
mice
in all groups
appeared
normal
until the
end
of the study period. However,
in the group receiving
unripened berries from
June, 1 or 3 necropsied
mice had erosion of the gastric
mucosa and 3 of 3
had severe villous atrophy in the small intestine. Necropsy
did not reveal
tissue
changes in the mice receiving
ripened
or unripened berries
from July.
These results
are summarized in Table ^.
DISCUSSION
The most consistent
sign of toxicity
due to solanaceous alkaloids is
gastroenteritis
with epigastric
pain, nausea, vomiting and diarrhea (17)
presumably
because
of solanine's saponin-like
activity (4,5). In addition,
systemic toxicity
consists
of bradycardia, weakness, central nervous
system
depression, headache, fever,
diaphoresis, dyspnea and respiratory
depression
(17). These
signs may be due, in part, to solanine's structural
resemblance

COLLINS
manner
me,
1989
week
of
I control
nal
Care
s for the
rg green
tely five
veloped
Lcamara
the end
t group
:he
end
:s from
3 of 3
reveal
n July.
oids
is
r (17)
Jition,
,ystem
ession
rlance
TOXICITY OF NIGHTSHADE
BERRIES
IN MICE 189
TABLE 1
Summary
of Results
Signs Of Solanine
Toxicity*
Behavioral Histoloqic*
*
August,
1988
Ripened
Berries
Unripened
Berries
June. 1989
Unripened Berries
July
, 1989
Ripened Berries
Unripened
Berries
0/12
3l12
0/12
0/12
0112
0/6
0/6
)/)
0/3
0/3
* n = 12
for each
group
** results
seen/number
necropsied
Mice
were
gavaged
with 8 gm/kg
of lyophilized
Solanum dulcamara
berries,
both
ripened
and unripened, collected at different times of the year
from 2
consecutive
growing
seasons. Unripened berry material from early in the
growing
season
produced gastrointestinal
lesions consistent with solanine
toxicity while green
berries
produced
only behavioral changes
in the latter
part
of the summer.
Ripened
berries
failed
to produced
any signs of toxicity
throughout
the study
period.
to cardiac
glycosides
(15) and the plant's
ability to inhibit cholinesterase
(18,19).
In addition, anticholinergic
(13)
and direct cholinergic
effects
(20)
have
been
reported
to be caused by Solanum spp.
The mice receiving
unripened
S. dulcamara
fruit from August,
L988
displayed
behavioral signs suggestive
of solanine toxicity;
however,
necropsy
failed
to demonstrate histologic
changes.
In contrast,
mice gavaged
with

190 HORNFELDT
AND COLLINS
green
berries from June, 1989 remained
behaviorally
normal while necropsy
results revealed
gastric
erosion and severe villous atrophy in the small
intestine,
a finding
which
suggests strong
intestinal irritation. In no case did
ripened
berries
produce
behavioral
or histologic
evidence of solanine toxicity.
One is tempted
to speculate that the
nature
of toxicity of S. dulcamara
berries changes during the course of the summer. Histologic changes
occurred
in mice receiving
green
berries, collected
in June when berries
first
became available,
and appear to be due to solanine's
saponin-like
activity.
These lesions
were absent
in the animals treated
in the latter part of the
summer where
the behavioral changes observed
may
be due to other causes
such
as anticholinesterase activity.
The relatively
mild signs of toxicity observed
in the present
study are
in contrast with previous
work done in hamsters
gavaged
with approximately
4 gm/kg
of dried
potato
sprouts.
Death
occurred
in the hamsters
beginning
5 hours
after dosing and by 24 hours
5 of 10 animals were dead. Gross
examination of dead hamsters during necropsy revealed severe
gastrointestinal
lesions consisting of thickened,
hemorrhagic
glandular
surfaces of the stomach,
and
red, hemorrhagic mucosa in the duodenum
and
jejunum. Microscopic
examination showed some degree of necrosis of the
gastric glandular
mucosa
and adjacent squamous
epithelium.
The
duodenum
also displayed necrosis
with loss of epithelium and villi. The jejunum
exhibited
blunting of villi.
The results
of this study suggest
a relatively nontoxic nature
of ripened
S.
dulcamara
berries. A dose of fresh
berries in a 30 pound
(13.6
kg) child
equivalent
to that received
by the mice
in this study
would be approximately
59
green
and
45 ripened
berries. It should be noted,
however,
that
this may
not be the case elsewhere. While little evidence
is offered, several
authorities
suggest
that local growing
conditions
may affect the amount of
solanine
present
in Solanum species
(4,5). However, it does appear that
locally,
children ingesting limited
amounts of these
berries
do not require
the
aggressive
treatment
they may currently receive. More studies
may
be
required
to fully assess the toxic
nature
of this
plant.
assist:

COLLINS
ecropsy
e small
rase
did
toxicity.
rcamara
changes
'ies
first
activity.
t of the
: causes
udy
are
:imately
ginning
Gross
severe
indular
rm
and
of the
denum
junum
.pened
) child
nately
is
may
everal
unt of
r that
re the
ay be
TOXIC]TY
OF NIGHTSHADE
BERRIES
IN MICE 191
ACKNOWLEDGEMENT
The authors are
grateful
to Dr. Alice A. Larson for valuable
editorial
assistance.
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